Foldamers with Heterogeneous Backbones

本工作的目的是制备具有确定和可预测构象的折叠物（非天然低聚物或生物聚合物）。他们将合成和构象分析许多异质低聚物，其中一种类型的单体（如α氨基酸）提供功能多样性，而另一种类型的单体（循环约束的β或γ氨基酸）提供构象特异性和稳定性。仅含有γ氨基酸的均相低聚物也将被合成和分析，由于单体立体化学变化而不均匀的低聚物也将被合成和分析。一旦确定了在水溶液中采用特定构象的新低聚物，将测试它们对蛋白水解降解的稳定性以及它们穿过活细胞膜的能力。有了这个奖项，有机和大分子化学项目支持了威斯康星大学化学系Samuel H. Gellman博士的研究。Gellman博士将探索利用天然和非天然氨基酸的组合合成新蛋白质。然后对这些蛋白质进行筛选，以寻找那些在水（水基）溶液中采用特定构象（形状）的蛋白质。那些折叠成特定和可预测形状的将被筛选它们对生物分子目标的亲和力。特别是，它们将被筛选是否有能力破坏其他蛋白质之间的相互作用。控制蛋白质-蛋白质相互作用的破坏可能在未来的生物医学科学中应用于癌症预防。通过本项目的培训，学生将获得生物有机和超分子有机化学方面的经验，因此他们将具备制药和特种化学品行业所需的技能。

The objective of this work is to prepare foldamers (unnatural oligomers or biopolymers) that adopt defined and predictable conformations. They will synthesize and conformationally analyze a number of heterogeneous oligomers where one type of monomer (such as alpha amino acids) provides functional diversity while another type of monomer (cyclically constrained beta or gamma amino acids) provides conformational specificity and stability. Homogeneous oligomers containing just gamma amino acids will also be synthesized and analyzed as will oligomers that are heterogeneous due to monomer stereochemistry variations. Once new oligomers are identified that adopt specific conformations in aqueous solutions, they will be tested for stability to proteolytic degradation and for their ability to move across membranes of living cells. With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Samuel H. Gellman of the Department of Chemistry at the University of Wisconsin. Dr. Gellman will explore the synthesis of new proteins using combinations of natural and unnatural amino acids. These proteins will then be screened to look for those which adopt specific conformations (shapes) in aqueous (water based) solutions. Those which do fold into specific and predictable shapes will be screened for their affinity to biomolecular targets. In particular, they will be screened for their ability to disrupt other protein-protein interactions. Controlled disruption of protein-protein interactions has possible future biomedical science applications in cancer prevention. Students trained as a result of working on this project will gain experience in bioorganic and supramolecular organic chemistry, hence they will have skills needed by the pharmaceutical and speciality chemicals industries.